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The Antiviral Activity Of Lichen Metabolites Against Dengue Virus, Naphat Loeanurit Jan 2020

The Antiviral Activity Of Lichen Metabolites Against Dengue Virus, Naphat Loeanurit

Chulalongkorn University Theses and Dissertations (Chula ETD)

Dengue fever is one of the mosquito-borne infectious diseases globally. Currently, no specific treatment was established. Depsidones and depsides are one of the most common lichen secondary metabolites produced for the organism’s survival in extreme environments. These compounds have been reported as antivirals against the other virus in Flaviviridae family, hepatitis C virus. In this study, depsidones and depsides were explored for anti-dengue efficacy and cellular toxicity. One depsidone, VK-0014, and two depsides, TT-031 and TT-032, exhibited an anti-DENV2 with effective concentration (EC50) of 17.42 ± 3.21, 2.43 ± 0.19, and 0.91 ± 0.15 µM, respectively. Cytotoxicity concentration (CC50) in …


Application Of Phage Display Technology For The Production Of Antibodies Againststreptococcus Suis Serotype 2, Pattarawadee Sulong Jan 2020

Application Of Phage Display Technology For The Production Of Antibodies Againststreptococcus Suis Serotype 2, Pattarawadee Sulong

Chulalongkorn University Theses and Dissertations (Chula ETD)

Streptococcus suis (S. suis) serotype 2 infection is problematic in the swine industry and responsible for most cases of human infection worldwide. Since current multiplex PCR cannot differentiate between serotypes 2 and 1/2, then serotype-specific antibodies (Abs) are required for serotype identification to confirm S. suis serotype 2 infection. This study aimed to generate Abs specific to S. suis serotype 2 by phage display from a human heavy chain variable domain (VH) antibody library. For biopanning, whole cells of S. suis serotype 2 were used as the target antigen. With increasing selection stringency, we could select the VH Abs that …


The Differential Dendritic Cell Properties In Response To Candida Albicans And Non-Albican Candida Β-Glucan, Truc Thi Huong Dinh Jan 2020

The Differential Dendritic Cell Properties In Response To Candida Albicans And Non-Albican Candida Β-Glucan, Truc Thi Huong Dinh

Chulalongkorn University Theses and Dissertations (Chula ETD)

Increased mortality and antifungal drug resistance of non-albicans Candidiasis patients have become an alarming in health problems nowadays, whereas profound knowledge of their pathogenesis mechanisms is still limited. The immune responses of innate and adaptive immunity play a crucial role in protecting from Candida infections. Dendritic cells (DCs) are the most notable because of their roles in bridging an innate immunity and specific adaptive immunity to eliminate fungal invasion. It is little known about DC functions in non-albicans Candida (NACs) infections. Besides, there is less study on evaluating the DC properties upon the interaction between DCs and NACs-derived ß-glucans. Therefore, …


Neutrophil Extracellular Traps (Nets) Formation Of Fcgr2b Deficient Mice In Lupus Mouse Model With Ischemic Reperfusion Injury, Wilasinee Saisorn Jan 2020

Neutrophil Extracellular Traps (Nets) Formation Of Fcgr2b Deficient Mice In Lupus Mouse Model With Ischemic Reperfusion Injury, Wilasinee Saisorn

Chulalongkorn University Theses and Dissertations (Chula ETD)

Acute kidney injury (AKI) caused by renal ischemic reperfusion (I/R) is the most prevalent cause of morbidity and mortality in patients. Neutrophil extracellular traps (NETs) are important for the progression of lupus nephritis after renal I/R injury. Because neutrophils are the first immune cell that respond to tissue damage, neutrophils might be an important cell that determines renal I/R injury. Additionally, NET components, including cell-free DNA, histone, nucleosome, and cytoplasmic protein compartment release the auto-antigens that accelerate lupus disease activity. Therefore, this project aimed to compare NETs formation in several internal organs following renal I/R injury in Fcgr2b deficient (Fcgr2b-/-) …


Classification Of Organoid Transcriptomic Profiles Unravelling Colorectal Cancer Molecular Subtypes, Pattarin Nuwongsri Jan 2020

Classification Of Organoid Transcriptomic Profiles Unravelling Colorectal Cancer Molecular Subtypes, Pattarin Nuwongsri

Chulalongkorn University Theses and Dissertations (Chula ETD)

Colorectal cancer (CRC) is genetically and transcriptomically heterogeneous disease. Molecular subtyping of colorectal cancer using consensus molecular subtype (CMS) system demonstrated the potential predictive value for tumor progression and treatment response. However, the CMS system was developed from data of whole tissues containing both cancer and non-tumor transcripts components for classification which does not directly represent intrinsic heterogeneity of cancer cells. In this study genetic profiles of CRC organoids were investigated first, and the results indicate chromosomal instability (CIN) and microsatellite instability (MSI) as pathogenic pathways of CRC. Furthermore, the results also revealed diverse patterns of somatic mutations of these …


Clinical Parameters And Biological Markers Associated With Acute Severe Ocular Complications In Stevens-Johnson Syndrome And Toxic Epidermal Necrolysis In Thailand, Rawiphan Panpruk Jan 2020

Clinical Parameters And Biological Markers Associated With Acute Severe Ocular Complications In Stevens-Johnson Syndrome And Toxic Epidermal Necrolysis In Thailand, Rawiphan Panpruk

Chulalongkorn University Theses and Dissertations (Chula ETD)

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse drug reactions with high mortality rates. Sequelae such as blindness remained even after recovery. Patients with SJS/TEN should be accurately diagnosed and received appropriate treatment as soon as possible. Therefore, factors for severity prediction are necessary. This study aimed to clarify clinical parameters and biological markers that can predict acute severe ocular complications (SOCs) in SJS/TEN. This retrospective cross-sectional study enrolled forty-seven SJS/TEN patients and divided them into two groups according to ocular severity at the acute onset, non-severe ocular complications group (N = 27) and severe ocular …


Over-Expression Of Mir-223 Induces M2 Macrophage Through Glycolysis Alteration And Attenuates Lipopolysaccharide-Induced Sepsis Mouse Model, A Proposal Sepsis Cell-Based Therapy, Dang Phi Cong Jan 2020

Over-Expression Of Mir-223 Induces M2 Macrophage Through Glycolysis Alteration And Attenuates Lipopolysaccharide-Induced Sepsis Mouse Model, A Proposal Sepsis Cell-Based Therapy, Dang Phi Cong

Chulalongkorn University Theses and Dissertations (Chula ETD)

Sepsis, a systemic infection with excessive inflammatory symptoms due to dysregulation of immune responses, remains the most concerned health-care problem worldwide with the mortality rate critically beyond the number of death cases in HIV, cancers or stroke. While it is well documented that pathogenesis of sepsis is intimately involved in dysregulation of macrophages, great effort has been made to discover efficacious therapy to control macrophage responses. However, macrophages are the most versatile immune cells with large spectrum of heterogeneous phenotypes and functions. Recently, collection of insights unravel the crucial role of metabolism as an orchestrator of immune regulation, intervention on …


Resistance To Ectromelia Virus Infection Requires Cgas In Bone Marrow-Derived Cells Which Can Be Bypassed With Cgamp Therapy., Eric B. Wong, Brian Montoya, Maria Ferez, Colby Stotesbury, Luis J. Sigal Dec 2019

Resistance To Ectromelia Virus Infection Requires Cgas In Bone Marrow-Derived Cells Which Can Be Bypassed With Cgamp Therapy., Eric B. Wong, Brian Montoya, Maria Ferez, Colby Stotesbury, Luis J. Sigal

Department of Microbiology and Immunology Faculty Papers

Cells sensing infection produce Type I interferons (IFN-I) to stimulate Interferon Stimulated Genes (ISGs) that confer resistance to viruses. During lympho-hematogenous spread of the mouse pathogen ectromelia virus (ECTV), the adaptor STING and the transcription factor IRF7 are required for IFN-I and ISG induction and resistance to ECTV. However, it is unknown which cells sense ECTV and which pathogen recognition receptor (PRR) upstream of STING is required for IFN-I and ISG induction. We found that cyclic-GMP-AMP (cGAMP) synthase (cGAS), a DNA-sensing PRR, is required in bone marrow-derived (BMD) but not in other cells for IFN-I and ISG induction and for …


Gasdermins In Apoptosis: New Players In An Old Game., Corey Rogers, Emad S. Alnemri Dec 2019

Gasdermins In Apoptosis: New Players In An Old Game., Corey Rogers, Emad S. Alnemri

Department of Biochemistry and Molecular Biology Faculty Papers

Apoptosis is a form of programmed cell death (PCD) that plays critical physiological roles in removing superfluous or dangerous cell populations that are unneeded or threatening to the health of the host organism. Although the molecular pathways leading to activation of the apoptotic program have been extensively studied and characterized starting in the 1970s, new evidence suggests that members of the gasdermin superfamily are novel pore-forming proteins that augment apoptosis by permeabilizing the mitochondria and participate in the final stages of the apoptotic program by inducing secondary necrosis/pyroptosis. These findings may explain outstanding questions in the field such as why …


The Histone Deacetylase Inhibitor Tubacin Mitigates Endothelial Dysfunction By Up-Regulating The Expression Of Endothelial Nitric Oxide Synthase., Jihui Chen, Jian Zhang, Noor F. Shaik, Bing Yi, Xin Wei, Xiao-Feng Yang, Ulhas P. Naik, Ross Summer, Guijun Yan, Xinyun Xu, Jianxin Sun Dec 2019

The Histone Deacetylase Inhibitor Tubacin Mitigates Endothelial Dysfunction By Up-Regulating The Expression Of Endothelial Nitric Oxide Synthase., Jihui Chen, Jian Zhang, Noor F. Shaik, Bing Yi, Xin Wei, Xiao-Feng Yang, Ulhas P. Naik, Ross Summer, Guijun Yan, Xinyun Xu, Jianxin Sun

Center for Translational Medicine Faculty Papers

Endothelial nitric oxide (NO) synthase (eNOS) plays a critical role in the maintenance of blood vessel homeostasis. Recent findings suggest that cytoskeletal dynamics play an essential role in regulating eNOS expression and activation. Here, we sought to test whether modulation of cytoskeletal dynamics through pharmacological regulation of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation affects eNOS expression and endothelial function in vitro and in vivo.Wefound that tubulin acetylation inducer (tubacin), a compound that appears to selectively inhibit HDAC6 activity, dramatically increased eNOS expression in several different endothelial cell lines, as determined by both immunoblotting and NO production assays. Mechanistically, we found …


Constraint And Trade-Offs Regulate Energy Expenditure During Childhood, Samuel S. Urlacher, J. Josh Snodgrass, Lara R. Dugas, Lawrence S. Sugiyama, Melissa A. Liebert Dec 2019

Constraint And Trade-Offs Regulate Energy Expenditure During Childhood, Samuel S. Urlacher, J. Josh Snodgrass, Lara R. Dugas, Lawrence S. Sugiyama, Melissa A. Liebert

Biostatistics Collaborative Core: Faculty Publications and Other Works

Children’s metabolic energy expenditure is central to evolutionary and epidemiological frameworks for understanding variation in human phenotype and health. Nonetheless, the impact of a physically active lifestyle and heavy burden of infectious disease on child metabolism remains unclear. Using energetic, activity, and biomarker measures, we show that Shuar forager-horticulturalist children of Amazonian Ecuador are ~25% more physically active and, in association with immune activity, have ~20% greater resting energy expenditure than children from industrial populations. Despite these differences, Shuar children’s total daily energy expenditure, measured using doubly labeled water, is indistinguishable from industrialized counterparts. Trade-offs in energy allocation between competing …


Single-Nuclei Rna-Seq On Human Retinal Tissue Provides Improved Transcriptome Profiling, Akbar Shakoor, Yumei Li, Sangbae Kim, Albert Vitale, Ivana Kim, Denise Morgan, Shaoheng Liang, Nathaniel Wu, Ken Chen, Margaret M Deangelis, Rui Chen Dec 2019

Single-Nuclei Rna-Seq On Human Retinal Tissue Provides Improved Transcriptome Profiling, Akbar Shakoor, Yumei Li, Sangbae Kim, Albert Vitale, Ivana Kim, Denise Morgan, Shaoheng Liang, Nathaniel Wu, Ken Chen, Margaret M Deangelis, Rui Chen

Faculty, Staff and Students Publications

Single-cell RNA-seq is a powerful tool in decoding the heterogeneity in complex tissues by generating transcriptomic profiles of the individual cell. Here, we report a single-nuclei RNA-seq (snRNA-seq) transcriptomic study on human retinal tissue, which is composed of multiple cell types with distinct functions. Six samples from three healthy donors are profiled and high-quality RNA-seq data is obtained for 5873 single nuclei. All major retinal cell types are observed and marker genes for each cell type are identified. The gene expression of the macular and peripheral retina is compared to each other at cell-type level. Furthermore, our dataset shows an …


Trade-Offs Between Survival And Reproduction In Starvation-Selected Drosophila Melanogaster, Tammara Beeghly Dec 2019

Trade-Offs Between Survival And Reproduction In Starvation-Selected Drosophila Melanogaster, Tammara Beeghly

UNLV Theses, Dissertations, Professional Papers, and Capstones

Evolutionary outcomes are demonstrated by traits that affect an organism’s schedule of reproduction and survival. These life history traits are reflected in an organism’s physiology, development and behavior. Environmental changes, such as availability of nutritional resources, can profoundly affect evolutionary outcomes of individuals and populations. When shortages arise, there will be trade-offs in the allocation of resources, where one trait prevails at the expense of another.

In the laboratory, we can mimic conditions in nature and study the specific effects of the conditions that we re-create. In our case, over 100 generations of Drosophila melanogaster have been selected for starvation …


Restructuring Of The Axon Initial Segment In Mouse Models Of Neurodevelopmental Disorders, Rachel Ali Rodriguez Dec 2019

Restructuring Of The Axon Initial Segment In Mouse Models Of Neurodevelopmental Disorders, Rachel Ali Rodriguez

UNLV Theses, Dissertations, Professional Papers, and Capstones

Neurodevelopmental disorders (NDDs) affect more than 36% of children in countries with low- and middle- incomes (Boivin, 2015; McCoy, 2016). Interestingly, these heterogeneous disorders share a high incidence of epileptic seizures, suggesting a shared pathology. Seizures result when neuronal firing activity becomes disturbed and neurons fire excessively or in unregulated patterns. A key site in the control of neuronal firing patterns is the axon initial segment (AIS), where the local density of proteins and the morphology of the AIS in part determine the firing of neurons. We hypothesized that a disruption in the morphology and/or composition of the AIS can …


Multiple Mitochondrial Thioesterases Have Distinct Tissue And Substrate Specificity And Coa Regulation, Suggesting Unique Functional Roles., Carmen Bekeova, Lauren Anderson-Pullinger, Kevin Boye, Felix Boos, Yana Sharpadskaya, Johannes M Herrmann, Erin L. Seifert Dec 2019

Multiple Mitochondrial Thioesterases Have Distinct Tissue And Substrate Specificity And Coa Regulation, Suggesting Unique Functional Roles., Carmen Bekeova, Lauren Anderson-Pullinger, Kevin Boye, Felix Boos, Yana Sharpadskaya, Johannes M Herrmann, Erin L. Seifert

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Acyl-CoA thioesterases (Acots) hydrolyze fatty acyl-CoA esters. Acots in the mitochondrial matrix are poised to mitigate β-oxidation overload and maintain CoA availability. Several Acots associate with mitochondria, but whether they all localize to the matrix, are redundant, or have different roles is unresolved. Here, we compared the suborganellar localization, activity, expression, and regulation among mitochondrial Acots (Acot2, -7, -9, and -13) in mitochondria from multiple mouse tissues and from a model of Acot2 depletion. Acot7, -9, and -13 localized to the matrix, joining Acot2 that was previously shown to localize there. Mitochondria from heart, skeletal muscle, brown adipose tissue, and …


Reattachment Of The Multifidus Tendon In Lumbar Surgery To Decrease Postoperative Back Pain: A Technical Note., Neil Klinger, Emre Yilmaz, Dia R Halalmeh, R Shane Tubbs, Marc D Moisi Dec 2019

Reattachment Of The Multifidus Tendon In Lumbar Surgery To Decrease Postoperative Back Pain: A Technical Note., Neil Klinger, Emre Yilmaz, Dia R Halalmeh, R Shane Tubbs, Marc D Moisi

Articles, Abstracts, and Reports

The posterior midline approach to the lumbar spine requires significant manipulation of the paraspinal muscles. Muscle detachment and retraction results in iatrogenic damage such as crush injury, devascularization, and denervation, all of which have been associated with postoperative pain. The muscle most directly affected by the posterior approach is the lumbar multifidus (LM), the largest and most medial of the deep lumbar paraspinal muscles. The effects of the posterior approach on the integrity of the LM is concerning, as multiple studies have demonstrated that intraoperative injuries sustained by the LM lead to postoperative muscle atrophy and potentially worsening low back …


Ultrafast Two-Photon Imaging Of A High-Gain Voltage Indicator In Awake Behaving Mice, Jonathan Bradley, Lagnajeet Pradhan, Benjamin Mathieu, Stephen W Evans, Simon Chamberland, Dongqing Shi, Renzhi Yang, Benjamin B Kim, Annick Ayon, Abdelali Jalil, François St-Pierre, Mark J Schnitzer, Guoqiang Bi, Katalin Toth, Jun Ding, Stéphane Dieudonné, Michael Z Lin Dec 2019

Ultrafast Two-Photon Imaging Of A High-Gain Voltage Indicator In Awake Behaving Mice, Jonathan Bradley, Lagnajeet Pradhan, Benjamin Mathieu, Stephen W Evans, Simon Chamberland, Dongqing Shi, Renzhi Yang, Benjamin B Kim, Annick Ayon, Abdelali Jalil, François St-Pierre, Mark J Schnitzer, Guoqiang Bi, Katalin Toth, Jun Ding, Stéphane Dieudonné, Michael Z Lin

Faculty, Staff and Students Publications

Optical interrogation of voltage in deep brain locations with cellular resolution would be immensely useful for understanding how neuronal circuits process information. Here, we report ASAP3, a genetically encoded voltage indicator with 51% fluorescence modulation by physiological voltages, submillisecond activation kinetics, and full responsivity under two-photon excitation. We also introduce an ultrafast local volume excitation (ULoVE) method for kilohertz-rate two-photon sampling in vivo with increased stability and sensitivity. Combining a soma-targeted ASAP3 variant and ULoVE, we show single-trial tracking of spikes and subthreshold events for minutes in deep locations, with subcellular resolution and with repeated sampling over days. In the …


An In-Depth Review Of Retinitis Pigmentosa Development And Pathologies Overtime In Patients, Abdul Harris Dec 2019

An In-Depth Review Of Retinitis Pigmentosa Development And Pathologies Overtime In Patients, Abdul Harris

Honors College Theses

Retinitis Pigmentosa is a disease which can cause blindness and affects around 2.5 million people worldwide. It is a disorder that has a multitude of ways of being inherited, such as autosomal dominant, autosomal recessive as well as X-linked and mitochondrial linked disorder. While some versions of RP may be syndromic (20%-30%), a majority of cases are in fact non-syndromic. The majority of non-syndromic cases inherited via autosomal dominant RP having RHO gene mutations, and X-linked means of inheritance having majority of patients with RPGR gene mutations. Ushers Syndrome, a syndromic version of retinitis pigmentosa and autosomal recessive RP having …


Interaction Of The Oncoprotein Transcription Factor Myc With Its Chromatin Cofactor Wdr5 Is Essential For Tumor Maintenance., Lance R. Thomas, Clare M. Adams, Jing Wang, April M. Weissmiller, Joy Creighton, Shelly L. Lorey, Qi Liu, Stephen W. Fesik, Christine M. Eischen, William P. Tansey Dec 2019

Interaction Of The Oncoprotein Transcription Factor Myc With Its Chromatin Cofactor Wdr5 Is Essential For Tumor Maintenance., Lance R. Thomas, Clare M. Adams, Jing Wang, April M. Weissmiller, Joy Creighton, Shelly L. Lorey, Qi Liu, Stephen W. Fesik, Christine M. Eischen, William P. Tansey

Department of Cancer Biology Faculty Papers

The oncoprotein transcription factor MYC is overexpressed in the majority of cancers. Key to its oncogenic activity is the ability of MYC to regulate gene expression patterns that drive and maintain the malignant state. MYC is also considered a validated anticancer target, but efforts to pharmacologically inhibit MYC have failed. The dependence of MYC on cofactors creates opportunities for therapeutic intervention, but for any cofactor this requires structural understanding of how the cofactor interacts with MYC, knowledge of the role it plays in MYC function, and demonstration that disrupting the cofactor interaction will cause existing cancers to regress. One cofactor …


Cannabinoids For The Treatment Of Chronic Headaches, Kevin Krivanek, Lucy K. Wagala, Brian Heilbronner, Kimberly Loughlin, David Kinder Dec 2019

Cannabinoids For The Treatment Of Chronic Headaches, Kevin Krivanek, Lucy K. Wagala, Brian Heilbronner, Kimberly Loughlin, David Kinder

Pharmacy and Wellness Review

Species of the Cannabis plant genus were among the earliest medicinal plants cultivated by man, with historical accounts of their medicinal uses dating back before the Common Era. Despite its current legal status, Cannabis has garnered nationwide attention as a therapeutic agent for various disease states, including chronic headaches, due to its medical indications as an antispastic, analgesic, antiemetic, neuroprotective and anti-inflammatory agent. Since headaches have a high prevalence in the American population and greatly impair simple daily aspects of living, chronic headaches have become a particular point of interest in regard to the therapeutic potential of Cannabis. Clinical trials …


Evaluation Of Tumor Necrosis Factor Alpha In Sleep-Deprived Menopausal- Induced Rats And The Impact On Bone Health, Nicole Ellsworth, Dwight Curry Iii, Cj Deleon, Frank Frisch Dec 2019

Evaluation Of Tumor Necrosis Factor Alpha In Sleep-Deprived Menopausal- Induced Rats And The Impact On Bone Health, Nicole Ellsworth, Dwight Curry Iii, Cj Deleon, Frank Frisch

Student Scholar Symposium Abstracts and Posters

Post-menopausal osteoporosis as a consequence of estrogen depletion is a growing concern for women in the United States. As more women take on executive positions and experience sleep deprivation, there is the potential for up regulation of pro-inflammatory cytokines, such as tumor necrosis factor alpha. It follows that the homeostatic imbalance of osteoclastic and osteoblastic activity leads to a greater risk of disease. Bisphosphonates generally, and Zolendronate specifically works by decreasing the number of osteoclasts. This current study investigated the impact of Zolendronate on the concentrations of tumor necrosis factor alpha-type (TNFɑ) in 32 ovariectomized Wistar rats. Throughout a five …


Alzheimer's And Amyloid Beta: Amyloidogenicity And Tauopathy Via Dyshomeostatic Interactions Of Amyloid Beta, Jordan Tillinghast Dec 2019

Alzheimer's And Amyloid Beta: Amyloidogenicity And Tauopathy Via Dyshomeostatic Interactions Of Amyloid Beta, Jordan Tillinghast

Senior Honors Theses

This paper reviews functions of Amyloid-β (Aβ) in healthy individuals compared to the consequences of aberrant Aβ in Alzheimer’s disease (AD). As extraneuronal Aβ accumulation and plaque formation are characteristics of AD, it is reasonable to infer a pivotal role for Aβ in AD pathogenesis. Establishing progress of the disease as well as the mechanism of neurodegeneration from AD have proven difficult (Selkoe, 1994). This thesis provides evidence suggesting the pathogenesis of AD is due to dysfunctional neuronal processes involving Aβ’s synaptic malfunction, abnormal interaction with tau, and disruption of neuronal homeostasis. Significant evidence demonstrates that AD symptoms are partially …


Langerhans Cells Orchestrate The Protective Antiviral Innate Immune Response In The Lymph Node., Eric B. Wong, Brian Montoya, Colby Stotesbury, Maria Ferez, Ren-Huan Xu, Luis J. Sigal Dec 2019

Langerhans Cells Orchestrate The Protective Antiviral Innate Immune Response In The Lymph Node., Eric B. Wong, Brian Montoya, Colby Stotesbury, Maria Ferez, Ren-Huan Xu, Luis J. Sigal

Department of Microbiology and Immunology Faculty Papers

During disseminating viral infections, a swift innate immune response (IIR) in the draining lymph node (dLN) that restricts systemic viral spread is critical for optimal resistance to disease. However, it is unclear how this IIR is orchestrated. We show that after footpad infection of mice with ectromelia virus, dendritic cells (DCs) highly expressing major histocompatibility complex class II (MHC class IIhi DCs), including CD207+ epidermal Langerhans cells (LCs), CD103+CD207+ double-positive dermal DCs (DP-DCs), and CD103−CD207− double-negative dermal DCs (DN-DCs) migrate to the dLN from the skin carrying virus. MHC class IIhi …


Allele-Specific Rna Interference Prevents Neuropathy In Charcot-Marie-Tooth Disease Type 2d Mouse Models., Kathryn H Morelli, Laurie B Griffin, Nettie K Pyne, Lindsay M Wallace, Allison M Fowler, Stephanie N Oprescu, Ryuichi Takase, Na Wei, Rebecca Meyer-Schuman, Dattatreya Mellacheruvu, Jacob O Kitzman, Samuel G Kocen, Timothy J Hines, Emily L Spaulding, James R Lupski, Alexey Nesvizhskii, Pedro Mancias, Ian J Butler, Xiang-Lei Yang, Ya-Ming Hou, Anthony Antonellis, Scott Q Harper, Robert W Burgess Dec 2019

Allele-Specific Rna Interference Prevents Neuropathy In Charcot-Marie-Tooth Disease Type 2d Mouse Models., Kathryn H Morelli, Laurie B Griffin, Nettie K Pyne, Lindsay M Wallace, Allison M Fowler, Stephanie N Oprescu, Ryuichi Takase, Na Wei, Rebecca Meyer-Schuman, Dattatreya Mellacheruvu, Jacob O Kitzman, Samuel G Kocen, Timothy J Hines, Emily L Spaulding, James R Lupski, Alexey Nesvizhskii, Pedro Mancias, Ian J Butler, Xiang-Lei Yang, Ya-Ming Hou, Anthony Antonellis, Scott Q Harper, Robert W Burgess

Department of Biochemistry and Molecular Biology Faculty Papers

Gene therapy approaches are being deployed to treat recessive genetic disorders by restoring the expression of mutated genes. However, the feasibility of these approaches for dominantly inherited diseases - where treatment may require reduction in the expression of a toxic mutant protein resulting from a gain-of-function allele - is unclear. Here we show the efficacy of allele-specific RNAi as a potential therapy for Charcot-Marie-Tooth disease type 2D (CMT2D), caused by dominant mutations in glycyl-tRNA synthetase (GARS). A de novo mutation in GARS was identified in a patient with a severe peripheral neuropathy, and a mouse model precisely recreating the mutation …


3d Vessel-Wall Virtual Histology Of Whole-Body Perfused Mice Using A Novel Heavy Element Stain, P. Joy Dunmore-Buyze, Charmainne Cruje, Zengxuan Nong, Jason J. Lee, John A. Kiernan, J. Geoffrey Pickering, Maria Drangova Dec 2019

3d Vessel-Wall Virtual Histology Of Whole-Body Perfused Mice Using A Novel Heavy Element Stain, P. Joy Dunmore-Buyze, Charmainne Cruje, Zengxuan Nong, Jason J. Lee, John A. Kiernan, J. Geoffrey Pickering, Maria Drangova

Medical Biophysics Publications

Virtual histology – utilizing high-resolution three-dimensional imaging – is becoming readily available. Micro-computed tomography (micro-CT) is widely available and is often coupled with x-ray attenuating histological stains that mark specific tissue components for 3D virtual histology. In this study we describe a new tri-element x-ray attenuating stain and perfusion protocol that provides micro-CT contrast of the entire vasculature of an intact mouse. The stain – derived from an established histology stain (Verhoeff’s) – is modified to enable perfusion through the vasculature; the attenuating elements of the stain are iodine, aluminum, and iron. After a 30-minute perfusion through the vasculature (10-minute …


A Macaque Connectome For Large-Scale Network Simulations In Thevirtualbrain, Kelly Shen, Gleb Bezgin, Michael Schirner, Petra Ritter, Stefan Everling, Anthony R. Mcintosh Dec 2019

A Macaque Connectome For Large-Scale Network Simulations In Thevirtualbrain, Kelly Shen, Gleb Bezgin, Michael Schirner, Petra Ritter, Stefan Everling, Anthony R. Mcintosh

Brain and Mind Institute Researchers' Publications

© 2019, The Author(s). Models of large-scale brain networks that are informed by the underlying anatomical connectivity contribute to our understanding of the mapping between the structure of the brain and its dynamical function. Connectome-based modelling is a promising approach to a more comprehensive understanding of brain function across spatial and temporal scales, but it must be constrained by multi-scale empirical data from animal models. Here we describe the construction of a macaque (Macaca mulatta and Macaca fascicularis) connectome for whole-cortex simulations in TheVirtualBrain, an open-source simulation platform. We take advantage of available axonal tract-tracing datasets and enhance the existing …


Predator-Induced Fear Causes Ptsd-Like Changes In The Brains And Behaviour Of Wild Animals, Liana Y. Zanette, Emma C. Hobbs, Lauren E. Witterick, Scott A. Macdougall-Shackleton, Michael Clinchy Dec 2019

Predator-Induced Fear Causes Ptsd-Like Changes In The Brains And Behaviour Of Wild Animals, Liana Y. Zanette, Emma C. Hobbs, Lauren E. Witterick, Scott A. Macdougall-Shackleton, Michael Clinchy

Brain and Mind Institute Researchers' Publications

© 2019, The Author(s). Predator-induced fear is both, one of the most common stressors employed in animal model studies of post-traumatic stress disorder (PTSD), and a major focus of research in ecology. There has been a growing discourse between these disciplines but no direct empirical linkage. We endeavoured to provide this empirical linkage by conducting experiments drawing upon the strengths of both disciplines. Exposure to a natural cue of predator danger (predator vocalizations), had enduring effects of at least 7 days duration involving both, a heightened sensitivity to predator danger (indicative of an enduring memory of fear), and elevated neuronal …


Cardiovascular Risk In Patients With Rheumatoid Arthritis: The Role Of Cholesterylester Transfer Protein, Ali M. Mursi, Emad M. Elshebiny, Lobna Y. Ebrahim, Sahar H. Quashwa, Sherry K. Abdelrahman, Taghreed F. Mohammed Mostafa Dec 2019

Cardiovascular Risk In Patients With Rheumatoid Arthritis: The Role Of Cholesterylester Transfer Protein, Ali M. Mursi, Emad M. Elshebiny, Lobna Y. Ebrahim, Sahar H. Quashwa, Sherry K. Abdelrahman, Taghreed F. Mohammed Mostafa

Journal of Medicine in Scientific Research

Aim To detect serum level of cholesterylester transfer protein (CETP) (the enzyme involved in reverse cholesterol transport) in patients with rheumatoid arthritis (RA) and to evaluate its relation to various clinical parameters of the disease, lipid profile, and carotid intima-media thickness (CIMT) as a marker of atherosclerosis and cardiovascular disease risk. Patients and methods This study involved a total of 80 participants, comprising 50 patients with RA and 30 age-matched and sex-matched healthy controls. Detailed medical history and thorough clinical examination (general and musculoskeletal) as well as laboratory investigations including lipid profile were performed for all patients with RA. Serum …


Influence Of Metabolic Capacity On The Consequences Of Spreading Depolarization, Katelyn M. Reinhart Dec 2019

Influence Of Metabolic Capacity On The Consequences Of Spreading Depolarization, Katelyn M. Reinhart

Biomedical Sciences ETDs

In the United States, stroke is the fifth leading cause of death and stroke survivors often face long-term disability. After ischemic stroke, the ischemic territory can expand and recruit previously viable tissues into the lesioned area. During this critical period, there is an unsettling lack of interventions that prevent or treat secondary neuronal loss and cognitive decline. Clinical subdural recordings have revealed a close link between infarct progression and waves of spreading depolarizations (SD) in the acutely injured brain. SD is a slowly progressing wave of near-complete neuroglia depolarization that is extremely energetically demanding and this additional metabolic ‘hit’ …


A Comparison Between Monopolar Radiofrequency Ablation And Electrocautery (Diathermy) Ablations In Left Modified Maze (Short-Term Results), Waleed El-Awady Dec 2019

A Comparison Between Monopolar Radiofrequency Ablation And Electrocautery (Diathermy) Ablations In Left Modified Maze (Short-Term Results), Waleed El-Awady

Journal of Medicine in Scientific Research

Introduction Atrial fibrillation is the most common cardiac arrhythmia and is associated with significant morbidity and mortality. The classic cut-and-sew maze procedure is successful in 85–95% of patients. However, it is technically challenging and requires prolonged cardiopulmonary bypass. The left modified maze procedure is successful in 65–85% of patients. The aim of this study was to compare the success of two different ablation sources in the left modified MAZE. Patients and methods Between June 2010 and December 2016, 40 patients underwent left modified MAZE (Cox III) procedure: 20 patients were done with monopolar radiofrequency ablation (group A) and the other …